S2631
Radiobiology - Tumour radiobiology
ESTRO 2026
intervals. To mark hypoxia and perfusion, mice were injected with pimonidazole 1 h and Hoechst 1 min prior to sacrifice, respectively. 24h after the last treatment, mice were sacrificed and tumor was harvested and snap-frozen for pimonidazole immunohistochemistry. Results: We previously demonstrated that MitoTam reduces hypoxia in tumor spheroids. Next, we investigated whether this observed alleviation also leads to increased DNA damage. Immunofluorescent staining showed γ H2AX expression following treatment with MitoTam and RT (Fig. 1A,C). Quantification of γ H2AX 2 h post-RT revealed that in both B16OVA and MOC1.3D5 spheroids, the combination of MitoTam with RT resulted in a significant increase in DNA damage compared to either treatment alone (B16OVA *p = 0.0004, #p = 0.0002, MOC1.3D5 *p = 0.0256, #p = 0.0019; Fig. 1B,D). Furthermore, MOC1.3D5 tumors from mice treated with MitoTam showed a significant decrease in the mean pimonidazole signal intensity compared to control (p = 0.016), indicating reduced tumor hypoxia. A zone analysis of the fraction of hypoxia also demonstrated a decrease in all zones indicating reduction of oxygen consumption, although not statistically significant (Fig. 2).
Conclusion: Treatment with MitoTam followed by RT increases γ H2AX expression in spheroids compared to either treatment alone, indicating an increase in radiosensitivity by MitoTam. In a pre-clinical study, administration of MitoTam via p.t. injections resulted in a decrease in hypoxia in MOC1.3D5 tumors. Future studies will investigate whether the observed OXPHOS inhibition-mediated alleviation of hypoxia translates to increased efficacy of RT in pre-clinical models. Keywords: MitoTam, Radiotherapy, OXPHOS Digital Poster Highlight 1823 METTL3-Mediated Epitranscriptomic Regulation Drives Pancreatic Acinar Cell Carcinoma Pathogenesis and Therapeutic Resistance Shotaro Tatekawa 1,2 , Tomoaki Hara 2 , Sikun Meng 2 , Tetsuya Sato 3,4 , Keisuke Tamari 1 , Masamitsu Konno 5 , Yuichiro Doki 6 , Hidetoshi Eguchi 6 , Kazuhiko Ogawa 1 , Hideshi Ishii 2 1 Department of Radiation Oncology, The University of Osaka Graduate School of Medicine, Osaka, Japan. 2 Department of Medical Data Science, The University of Osaka Graduate School of Medicine, Osaka, Japan. 3 Biomedical Research Center, Faculty of Medicine, Saitama Medical University, Saitama, Japan. 4 H.U.
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